Van Zandt was born in Franklin County, Tennessee in the United States to Jacob and Mary Isaacs Van Zandt. The Van Zandt family had migrated to America from Holland prior to the American Revolutionary War.[1] In 1833 he married Frances Lipscomb and went into a joint business venture with his father by opening a store. Van Zandt later moved to Coffeeville, Mississippi, where he opened his own store. After experiencing financial difficulties after the depression of 1837, Van Zandt became interested in a debate society which enabled him to use his natural talent for public speaking. This spurred an interest in law and within a year he was a member of the Mississippibar.

Van Zandt was the representative of Harrison County in the House of Representatives of the Republic of Texas from 1840 until 1842, when Sam Houston appointed him Republic of Texas Chargé d'Affaires in Washington, DC. In 1841 Van Zandt donated land, along with Peter Whetestone, to create a county seat for Harrison County. Van Zandt named the new city in honor of the Chief Justice of the U.S. Supreme CourtJohn Marshall. As the Republic of Texas ambassador to the United States Van Zandt was instrumental in crafting the Annexation Treaty of the Republic of Texas to the U.S.

He returned to Texas in 1845 to serve as a delegate to the Texas state constitutional convention. Van Zandt died during a yellow fever epidemic in Houston while campaigning for governor in 1847.